• No se han encontrado resultados

Atrazine in drinking-water

N/A
N/A
Protected

Academic year: 2020

Share "Atrazine in drinking-water"

Copied!
10
0
0

Texto completo

(1)

WHO/SDE/WSH/03.04/32 English only

Atrazine in Drinking-water

Background document for development of

WHO

Guidelines for Drinking-water Quality

______________________________

(2)

© World Health Organization 2003

All rights reserved. Publications of the World Health Organization can be obtained from Marketing and Dissemination, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel: +41 22 791 2476; fax: +41 22 791 4857; email: bookorders@who.int). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to Publications, at the above address (fax: +41 22 791 4806; email: permissions@who.int).

The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.

The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.

(3)

Preface

One of the primary goals of WHO and its member states is that “all people, whatever

their stage of development and their social and economic conditions, have the right to

have access to an adequate supply of safe drinking water.” A major WHO function to

achieve such goals is the responsibility “to propose regulations, and to make

recommendations with respect to international health matters ....”

The first WHO document dealing specifically with public drinking-water quality was

published in 1958 as International Standards for Drinking-Water. It was subsequently

revised in 1963 and in 1971 under the same title. In 1984–1985, the first edition of the

WHO Guidelines for drinking-water quality (GDWQ) was published in three

volumes: Volume 1, Recommendations; Volume 2, Health criteria and other

supporting information; and Volume 3, Surveillance and control of community

supplies. Second editions of these volumes were published in 1993, 1996 and 1997,

respectively. Addenda to Volumes 1 and 2 of the second edition were published in

1998, addressing selected chemicals. An addendum on microbiological aspects

reviewing selected microorganisms was published in 2002

.

The GDWQ are subject to a rolling revision process. Through this process, microbial,

chemical and radiological aspects of drinking-water are subject to periodic review,

and documentation related to aspects of protection and control of public

drinking-water quality is accordingly prepared/updated.

Since the first edition of the GDWQ, WHO has published information on health

criteria and other supporting information to the GDWQ, describing the approaches

used in deriving guideline values and presenting critical reviews and evaluations of

the effects on human health of the substances or contaminants examined in

drinking-water.

For each chemical contaminant or substance considered, a lead institution prepared a

health criteria document evaluating the risks for human health from exposure to the

particular chemical in drinking-water. Institutions from Canada, Denmark, Finland,

France, Germany, Italy, Japan, Netherlands, Norway, Poland, Sweden, United

Kingdom and United States of America prepared the requested health criteria

documents.

Under the responsibility of the coordinators for a group of chemicals considered in the

guidelines, the draft health criteria documents were submitted to a number of

scientific institutions and selected experts for peer review. Comments were taken into

consideration by the coordinators and authors before the documents were submitted

for final evaluation by the experts meetings. A “final task force” meeting reviewed the

health risk assessments and public and peer review comments and, where appropriate,

decided upon guideline values. During preparation of the third edition of the GDWQ,

it was decided to include a public review via the world wide web in the process of

development of the health criteria documents.

(4)

Criteria monographs and Concise International Chemical Assessment Documents, the

International Agency for Research on Cancer, the joint FAO/WHO Meetings on

Pesticide Residues, and the joint FAO/WHO Expert Committee on Food Additives

(which evaluates contaminants such as lead, cadmium, nitrate and nitrite in addition to

food additives).

(5)

Acknowledgements

The work of the following coordinators was crucial in the development of this

background document for development of WHO

Guidelines for drinking-water

quality

:

J.K. Fawell, Water Research Centre, United Kingdom

(inorganic constituents)

U. Lund, Water Quality Institute, Denmark

(organic constituents and pesticides)

B. Mintz, Environmental Protection Agency, USA

(disinfectants and disinfectant by-products)

The WHO coordinators were as follows:

Headquarters

:

H. Galal-Gorchev, International Programme on Chemical Safety

R. Helmer, Division of Environmental Health

Regional Office for Europe

:

X. Bonnefoy, Environment and Health

O. Espinoza, Environment and Health

Ms Marla Sheffer of Ottawa, Canada, was responsible for the scientific editing of the

document.

The efforts of all who helped in the preparation and finalization of this document,

including those who drafted and peer reviewed drafts, are gratefully acknowledged.

The convening of the experts meetings was made possible by the financial support afforded to WHO by the Danish International Development Agency (DANIDA), Norwegian Agency for Development Cooperation (NORAD), the United Kingdom Overseas Development

(6)

1

GENERAL DESCRIPTION

Identity

CAS no.: 1912-24-9

Molecular formula: C8H14ClN5

The IUPAC name for atrazine is 6-chloro-N-ethyl-N'-isopropyl-1,3,5-triazine-2,4-diamine or 2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine (1). Most commercial atrazine products are about 95% pure. Common impurities include sodium chloride and other symmetric triazines, such as simazine and propazine.

Physicochemical properties (1–3)

Property Value

Melting point 175–177 °C

Density 1.187 g/cm3 at 20 °C

Water solubility 30 mg/litre at 20 °C Log octanol–water partition

coefficient

2.3

Vapour pressure 40 × 10-6 Pa at 20 °C

Major uses

Atrazine is used as a selective pre- and post-emergence herbicide for the control of weeds in asparagus, maize, sorghum, sugar-cane, and pineapple. It is also used in forestry and for non-selective weed control on non-crop areas (1). Several countries have restricted its use.

Environmental fate

Atrazine can be degraded in surface water by photolysis and microorganisms via N

-dealkylation and hydrolysis of the chloro substituent; the corresponding half-lives are greater than 100 days at 20 °C. Hydrolysis and microbial degradation also take place in soil,

depending mainly on temperature, moisture, and pH. Half-lives of 20–50 days at 20–25 °C have been found under laboratory conditions, increasing at lower temperatures (4). These are similar to the half-lives found under natural conditions, but longer half-lives have been seen under special conditions (5). Degradation rates normally decrease with increasing depth, and atrazine can be fairly stable in groundwater (6).

Atrazine's degradation products in soil include 2-chloro-4-amino-6-isopropylamino-1,3,5-triazine, 2-chloro-4-ethylamino-6-amino-1,3,5-2-chloro-4-amino-6-isopropylamino-1,3,5-triazine, 2-chloro-4-amino-6-amino-1,3,5-triazine, 2-hydroxy-4-ethylamino-6-isopropylamino-1,3,5-2-chloro-4-amino-6-amino-1,3,5-triazine, and 2-hydroxy-4-amino-6-isopropylamino-1,3,5-triazine (the main metabolite) (7). Unsubstituted amino metabolites and triazine are formed later and may be mineralized completely. Atrazine and its dealkylated metabolites are moderately to very mobile in sandy, silt, and clay soils (8). Hydroxytriazines, however, are of low mobility (9) and persist for long periods in the soil (10).

ANALYTICAL METHODS

(7)

2

ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

Air

Evaporation tests in fields treated with atrazine have shown a loss of about 0.2% of the dose per day. It is found in precipitation just after spraying (11) and may then also be expected to be found in air.

Water

In many countries, after application in agricultural areas, atrazine has been found in

groundwater at levels of 0.01–6 µg/litre. It has also been detected in drinking-water in several countries at levels of 0.01–5 µg/litre (11,12).

Food

Hydroxy metabolites of atrazine have been found in plants grown in soil treated with it (10), but atrazine itself has not been found on crops. When sprayed on maize, it is quickly

transformed by the plant into its hydroxy metabolites (13).

KINETICS AND METABOLISM IN LABORATORY ANIMALS AND HUMANS

Atrazine appears to be readily absorbed from the gastrointestinal tract. In a study of rats given a single dose by gavage, at least 80% of the dose was absorbed. Within 3 days, 66% of the dose was excreted in the urine, 14% was retained in tissues, mainly the blood cells, and only 0.1% was found in the expired air (14). Doses given orally are retained mainly in

erythrocytes, liver, spleen, and kidney. Most of the metabolites found in soil can also be found as degradation products in rats, with 2-chloro-4,6-diamino-1,3,5-triazine being the major compound present in urine (15). Absorption through skin is limited, amounting to less than 2% after a 10-h exposure (16).

EFFECTS IN LABORATORY ANIMALS AND IN VITRO TEST SYSTEMS

Acute exposure

When technical atrazine (97% active ingredient) was administered to very young rats (<7 weeks), LD50s of 1900–2300 mg/kg of body weight were found, whereas LD50s in the range

670–740 mg/kg of body weight were found for 3-month-old rats (17). LD50s of 1750–4000

mg/kg of body weight were established in mice (18).

Atrazine causes moderate irritation to rabbit skin but is not appreciably irritating to the rabbit eye. It causes dermal sensitization in the guinea-pig. The dermal LD50 was reported to be

higher than 3100 mg/kg of body weight in the rat (19).

Short-term exposure

A 2-week study on female rats on oral toxicity and hormonal effects showed that 100 mg/kg of body weight per day influenced the serum concentration of estrogen, luteinizing hormone, prolactin, and progesterone. These effects may be important in the development of breast cancer in rats (20).

Long-term exposure

(8)

3

to cardiac toxicity after only 17 weeks. Treatment-related changes in haematological values were also reported in males of this group. Slight decreases in total serum protein and albumin were reported for males at 34 mg/kg of body weight per day. The NOAEL in this study was 5 mg/kg of body weight per day (21).

Technical atrazine (98.9% active ingredient) was fed to Sprague-Dawley rats for 2 years at 0, 10, 70, 500, or 1000 mg/kg in the diet. At 500 and 1000 mg/kg, there was a significant decrease in mean body weights of both sexes and decreased food consumption. At 1000 mg/kg, females were found to have a consistent reduction in red blood cell count,

haemoglobin and haematocrit, and glucose levels were depressed in both females and males during the first 12 months. The NOAEL in this study was 70 mg/kg (equivalent to 3.5 mg/kg of body weight per day) based on non-neoplastic effects as well as reduced body weight and food consumption (22).

Reproductive toxicity, embryotoxicity, and teratogenicity

In a two-generation rat study utilizing technical atrazine (97% active ingredient) in doses of 0, 0.5, 2.5, or 25 mg/kg of body weight per day, pup weights in the second generation at the two highest doses were statistically significantly lower than those of the control group. Both parental animals had significant decreases in body weight, body weight gain, and food consumption at 25 mg/kg of body weight per day. In addition, a statistically significant increase in relative testis weight was seen in both generations at this dose level. Thus, the reproductive NOAEL was 0.5 mg/kg of body weight per day, and the parental NOAEL 2.5 mg/kg of body weight per day (23).

No teratogenic response was found in New Zealand white rabbits that received atrazine by gavage on days 7–19 of gestation at dose levels of 1, 5, or 75 mg/kg of body weight per day. Maternal toxicity, in the form of decreased body weight gain and food consumption, was seen in the mid- and high-dose groups. Fetotoxicity was demonstrated only at 75 mg/kg of body weight per day by an increased resorption rate, reduced fetal weights, and delay of

ossification. The embryotoxic NOAEL appears to be 5 mg/kg of body weight per day, and the maternal NOAEL is 1 mg/kg of body weight per day (24).

Mutagenicity and related end-points

Atrazine has been tested in several systems, but there is no convincing evidence that it has any significant genotoxic action. However, deficiencies exist with respect to certain of the tests performed, and some evidence of genotoxic effects in vivo needs confirmation (25–28).

Carcinogenicity

In the study in which technical atrazine (98.9% active ingredient) was fed to Sprague-Dawley rats for 2 years at 0, 10, 70, 500, or 1000 mg/kg in the diet, a significant increase in the incidence of mammary tumours in females was seen at the three highest doses (22). The doses in the middle of the range (70 and 500 mg/kg) showed 95% significance for the occurrence of adenocarcinomas and carcinosarcomas, suggesting that atrazine interferes with hormonal regulation in male rats. The effect of atrazine on rat hormones confirms this hypothesis (20). The NOAEL in this study was 10 mg/kg, equivalent to 0.5 mg/kg of body weight per day. Studies on mice have not shown any signs of tumours (29).

EFFECTS ON HUMANS

(9)

4

GUIDELINE VALUE

The weight of evidence from a wide variety of genotoxicity assays indicates that atrazine is not genotoxic. There is some evidence that it can induce mammary tumours in rats as a result of hormonal changes, but it is highly probable that the mechanism for this process is non-genotoxic. No significant increase in neoplasia has been observed in mice. IARC has

concluded that atrazine is not classifiable as to its carcinogenicity in humans (Group 3) (31).

A TDI approach can therefore be used to calculate a guideline value. Based on a NOAEL of 0.5 mg/kg of body weight per day in a carcinogenicity study in the rat (22) and using an uncertainty factor of 1000 (100 for inter- and intraspecies variation and 10 to reflect potential neoplasia), a TDI of 0.5 µg/kg of body weight can be calculated. With an allocation of 10% of the TDI to drinking-water, the guideline value is 2 µg/litre (rounded figure).

REFERENCES

1. Worthing CR, ed. The pesticide manual, 9th ed. Farnham, British Crop Protection Council, 1991.

2. Meister R, ed. Farm chemicals handbook. Willoughby, OH, Meister Publishing, 1989. 3. Royal Society of Chemistry. The agrochemicals handbook, 3rd ed.Cambridge, 1991. 4. US Environmental Protection Agency. Method 525. Determination of organic compounds in drinking water by liquid-solid extraction and capillary column gas chromatography/mass spectrometry. In: Methods for the determination of organic compounds in drinking water. Cincinnati, OH, Environmental Monitoring Systems Laboratory, 1988:325-356 (EPA Report No. EPA-600/4-88/039; US NTIS PB89-220461).

5. Schoen SR, Winterlin WR. The effect of various soil factors and amendments on the degradation of pesticide mixtures. Journal of environmental science and health, Series B, 1987, 22(3):347-377.

6. Burnside OC, Fenster CR, Wicks GA. Dissipation and leaching of monuron, simazine and atrazine in Nebraska soils. Weeds, 1963, 11:209-213 (cited in Roeth FW, Lavy TL, Burnside OC. Atrazine degradation in two soil profiles. Weed science, 1969, 17:202-205).

7. Keller A. Degradation of atrazine (Gesaprim) in soil under aerobic/anaerobic conditions. Basel, Ciba-Geigy, 1978 (unpublished report 25/78).

8. Determination of the mobility of atrazine in selected soils by thin layer chromatography.

Basel, Ciba-Geigy, 1986 (Hazleton report, Study No. 6015-300).

9. Helling CS. Pesticide mobility in soil. II. Application of soil thin-layer chromatography.

Proceedings of the Soil Science Society of America, 1971, 35:737-748.

10. Kahn SU, Saidak WJ. Residues of atrazine and its metabolites after prolonged usage.

Weed research, 1981, 21:9-12.

11. Mair DCG, Yoo JY, Baker BE. Residues of atrazine and N-dealkylated atrazine in water from five agricultural watersheds in Quebec. Archives of environmental contamination and toxicology, 1978, 7:221-225.

12. Funari E et al. Preliminary report on the atrazine and molinate water supply contamination in Italy. Chemosphere, 1989, 18:2339-2343.

13. Shimabukuro RH. Atrazine metabolism in resistant corn and sorghum. Plant physiology, 1968, 43:1925-1930.

14. Bakke JE, Larson JD, Price CE. Metabolism of atrazine and 2-hydroxy-atrazine by the rat.

Journal of agricultural and food chemistry, 1972, 20:602-607.

15. Disposition of atrazine in the rat (general metabolism). Characterization and

identification of atrazine metabolites from rat urine (general metabolism) (addendum). Basel, Ciba-Geigy, 1987 (unpublished reports).

16. Dermal absorption of 14C-atrazine in rats. Basel, Ciba-Geigy, 1987 (unpublished report). 17. Gaines TB, Linder RE. Acute toxicity of pesticides in adult and weanling rats.

(10)

5

18. Acute oral LD50 of technical atrazine (G 30027) in the mouse. Basel, Ciba-Geigy, 1975 (unpublished report).

19. Dermal irritation study carried out by Hazleton Laboratories America, May 1975, and primary eye irritation study by Instituto Di Richerche, December 1976. Basel, Ciba-Geigy, 1975-1976 (unpublished reports, reviewed by the Office of Pesticide Programs of the US Environmental Protection Agency, Toxicology Chapter of the Registration Standard for Atrazine, 1989).

20. Kniewald J, Mildner P, Kniewald Z. Effects of s-triazine herbicides on hormone-receptor complex formation, 5a-reductase and 3a-hydroxysteroid dehydrogenase activity at the anterior pituitary level. Journal of steroid biochemistry, 1979, 11:833-838.

21. Atrazine technical—52 week oral feeding study in dogs. Basel, Ciba-Geigy, 1987 (unpublished report).

22. Twenty-four month combined oral toxicity and oncogenicity study in rats utilizing atrazine technical. Basel, Ciba-Geigy, 1986 (unpublished report).

23. 2-Generation rat reproduction study. Basel, Ciba-Geigy, 1987 (unpublished report). 24. Rabbit teratology study. Basel, Ciba-Geigy, 1984 (unpublished report).

25. Ames' test. Basel, Ciba-Geigy, 1986 (unpublished report).

26. Mutagenicity studies conducted by the Nomura Research Institute (Japan). Basel, Ciba-Geigy, 1979 (unpublished report).

27. Adler ID. A review of the coordinated research effort on the comparison of test systems for the detection of mutagenic effects, sponsored by the EEC. Mutation research, 1980, 74:77-93.

28. Micronucleus assay in mice. Basel, Ciba-Geigy, 1988 (unpublished report).

29. Atrazine-technical: 91 week oral carcinogenicity study in mice. Basel, Ciba-Geigy, 1986 (unpublished report).

30. Donna A et al. Triazine herbicides and ovarian epithelial neoplasms. Scandinavian journal of work, environment and health, 1989, 15(1):47-53.

Referencias

Documento similar

The idea of associating a vector bundle on the complex projective plane P 2 C to the three ltrations which form a mixed Hodge structure has a a dou- ble origin: Simpson's

The expression ((having become common since the spring)) -the French original reads ((etant devenues populaires des le printems»- refers to the spring of 1708 and is

The Global Compact for Safe, Orderly and Regular Migration (Global Compact for Migration hereinafter) has been considered the first instrument to comprehensively address all

 The expansionary monetary policy measures have had a negative impact on net interest margins both via the reduction in interest rates and –less powerfully- the flattening of the

Jointly estimate this entry game with several outcome equations (fees/rates, credit limits) for bank accounts, credit cards and lines of credit. Use simulation methods to

In our sample, 2890 deals were issued by less reputable underwriters (i.e. a weighted syndication underwriting reputation share below the share of the 7 th largest underwriter

The employed concentrations in other models are variable, ranging from 0.1 mg/mL employed in a model of ear inflammation in a rat model (Horvath et al., 2012) to 15 mg per day in

Experimental infections in susceptible BALB/c mice treated with 2.5 mg/kg body weight/day once every other day for a total of 15 days showed that indotecan cleared more than 80% of